key: cord-278225-d0gxb6bx
authors: Meng, Yifan; Guo, Ensong; Liu, Jia; Huang, Xiaoyuan; Sun, Chaoyang; Wu, Peng; Chen, Gang
title: Value and Challenges: Nucleic Acid Amplification Tests for SARS–CoV-2 in Hospitalized COVID-19 Patients
date: 2020-04-30
journal: J Infect
DOI: 10.1016/j.jinf.2020.04.036
sha: 
doc_id: 278225
cord_uid: d0gxb6bx

nan

To date, most countries have confirmed COVID-19 cases of person-to-person spread, and the number of confirmed cases worldwide is expected to continue to increase. It has been emphasized that diagnostic testing for SARS-CoV-2 was an especially important tool in the diagnosis and management of patients with COVID-19. 2 We included 3232 consecutive patients with COVID-19 who were hospitalized between January 18 th and March 27 th , 2020 (data cutoff date) at Tongji Hospital, a designated hospital for severe COVID-19 patients in Wuhan, China. All patients included in the present study were verified as positive for SARS-CoV-2 infection by reverse transcriptase polymerase chain reaction (RT-PCR). The specific operation methods were 3 followed according to the instructions and were consistent with other literature. 3, 4 According to the COVID-19 diagnosis and treatment plan issued by the National Health Commission, all patients included were diagnosed as moderate to severe cases. Clinical data were collected from medical records. The Ethical Committee of Tongji Hospital of Tongji Medical College at Huazhong University of Science and Technology approved this study (TJ-IRB20200311). Written informed consent was not obtained because the data were analyzed retrospectively and anonymously.

As of March 27th 2020, 3075 of these patients had at least one RT-PCR test during hospitalization, contributing 12 110 results. In total, 10 309 oropharyngeal swabs (OP) from 3003 patients and 1141 nasopharyngeal swabs (NP) from 567 patients were tested.

In addition, there were 660 specimens by other sampling methods (e.g., bronchoalveolar lavage fluid, anal swabs) being collected and tested. The overall positive rate of NP was 18.1% (207/1141), which was higher than that of OP (16.7%, 1718/10 314). The positive rates also differed between patients who were died and discharged (37.0% vs. 16.0%). It should be noted that only 42.5% of death cases (62/146) were tested positive in the last RT-PCR test before death. The average intervals between two viral tests during hospital stay were 6.2 days for death cases, with 6.0 days for survivors. Currently, the US CDC recommended collecting only NP, 5 while current public health England guidance advises samples from the upper respiratory tract should be sought as NP, OP, or both in combination. 6 In the present study, the overall positive rate of NP was higher than that of OP. We also evaluated the proportion of false-negative results (negatives between two positive results during hospitalization) among all negative results. 7 The false-negative rate of OP was 10.0% (863/8596), while NP was 8.4% (78/934). However, three patients 4 have contributed 33 false-negative oropharyngeal swabs (33/78), indicating significant individual bias. Here we suggested that the nasopharyngeal specimen is the preferred choice for swab-based SARS-CoV-2 testing with higher sensibility and specificity.

Moreover, the negative predictive value of viral tests should be carefully evaluated. At present clinical practice, patients with improved respiratory symptoms, improved pulmonary imaging, and nucleic acid tests negative twice consecutively (sampling interval ≥ 24 hours) can be discharged. However, the data showed that people can test positive for the virus even after two consecutive negative results. Pan et al. reported that potential false-negative nucleic acid testing results for SARS-CoV-2 could be caused by thermal inactivation of samples with low viral loads. 8 According to our study, repeated viral RT-PCR testing separated by prolonged duration is needed for viral clearance evaluation. Other immunological parameters or antibody test should also be used in combined with RT-PCR negative test. Negative results must be interpreted with clinical observations, patient history, and epidemiological information.

For 2876 survivors, SARS-CoV-2 infection persistence curves were generated based on Kaplan-Meier analysis (Figure) . The median duration from onset of symptoms to pathogens clearance was 24 days (IQR 17-33). The median duration from hospital admission to pathogens clearance was 8 days (IQR 3-14) . For patients with reliable preadmission pathogens-identified records, the median duration from pathogens identified to pathogens clearance was 16 days (IQR 11-24). Generally, it takes a person several days to weeks to show symptoms after being exposed to the virus. Our analysis indicated that the median duration from onset of symptoms to hospital admission was 16 days in Wuhan, China. The clinical sampling frequency for inpatients with COVID-19 should be 

Viral dynamics of SARS-CoV-2 across a spectrum of disease severity in COVID-19

Report from the American Society for

Value of Diagnostic Testing for SARS-CoV-2/COVID-19

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

COVID-19)

Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19

Potential false-negative nucleic acid testing results for Severe Acute Respiratory Syndrome Coronavirus 2 from thermal inactivation of samples with low viral loads

We would like to show our great respect to all the workers and volunteers in the fight against COVID-19, especially to the medical workers who work with the authors on the frontline.

None.

All authors declare that they have no financial or other conflicts of interest. 7